This invention relates to microfluidic devices that as can be used for carrying out analysis of biological samples, such as blood, urine and the like. More particularly, the invention relates to the materials for such devices and to their construction.
Microfluidic devices have been the subject of many patents and patent applications. The general principles of microfluidic devices of the present invention have been discussed in U.S. patent application Ser. No. 10/082,415 and more specific features of such devices are the subject of other applications. Such microfluidic devices include very small chambers containing liquid or solid reagents which contact liquid samples as they move through the device via capillary passageways, typically by capillary forces or applied centrifugal force (although other means of moving liquid have been disclosed and could be used in some microfluidic devices). After a small sample of liquid is added, the desired quantity of the sample is metered and then passed through one or more chambers where it meets reagents that prepare the sample for subsequent reaction or that react with an analyte in the sample to produce a detectable response, for example, a change in color.
Microfluidic devices have many advantages over the use of dry reagent strips for testing in the near-patient environment. However, the use of very small samples, say up to about 20 microliters, means that the interaction of the sample with the walls of the device is critical to its performance. The sample must be moved in the desired amounts through the capillaries and chambers and must contact dry reagents uniformly, while purging the air that initially filled the spaces in the device. Such problems have been considered in other patent applications and need not be discussed further here. The present invention is concerned with problems related to practical applications of microfluidic devices, particularly those containing liquid or dry reagents and in which ease of use and shelf life of the devices are important to their success.
Microfluidic devices can be made, but then not loaded with reagents agents until the time arrives when they are to be used. Such a method has the advantage of assuring that active reagents are used. However, loading the microfluidic device manually with very small amounts of reagents may be difficult to do with precision and could lead to inaccurate analytical results. Therefore, the present inventors believed that fully-functional microfluidic devices would be preferred by their users. That is, the devices should be pre-loaded with reagents and ready to use with minimal preparation. Doing so introduces significant problems, which will be addressed herein.
It will be evident that a microfluidic device must be keep free of contamination by materials which could prevent it from functioning in its intended manner. It is particularly important to protect the reagents with which the device has been loaded. In some types of analysis, only dry reagents are used. These must be protected from degradation by reaction with the surrounding atmosphere in order to assure that when used, perhaps several years after being manufactured, the reagents perform as intended, providing accurate results. Protection against moisture infiltration is of particular importance.
In other chambers, liquid reagents, diluents, buffers and the like may be loaded into the microfluidic device. Such liquids must be protected from contamination and from change in reagent concentration by loss of solvents and water. An advantage of microfluidic devices is their inherent ability to keep reagents separated until used. Thus, it is important also that liquid reagents not be allowed to migrate from the chambers in which they are loaded. Since the devices are small and the samples and reagents are of the microliter size, it will be evident that packaging of the devices is an important consideration, if they are to have acceptable shelf life and reliably provide accurate results.
The present inventors have considered these problems and propose the solutions presented in the following description.